Survival with bone marrow transplantation versus hydroxyurea or interferon for chronic myelogenous leukemia. The German CML Study Group.
Hydroxyurea, interferon, and HLA-identical sibling bone marrow transplantation are common therapies for chronic myelogenous leukemia (CML) in chronic phase. Which is best is controversial. The purpose of this study was to compare survival of patients with CML receiving HLA-identical sibling transplants versus hydroxyurea or interferon. The transplant cohort included 548 recipients of HLA-identical sibling transplants, reported to the International Bone Marrow Transplant Registry. The nontransplant cohort included 196 patients receiving hydroxyurea (n = 121) or interferon (n = 75) on a randomized trial of the German CML Study Group. Survivals were compared using proportional hazards regression with fixed and time-dependent variables to adjust for patient differences and changing risks over time. For the first 18 months after diagnosis, mortality was higher in the transplant than the nontransplant cohort (relative risk [RR], 5.85; P < .0001). From 18 to 56 months, mortality was similar (RR, 0.80; P = .38). After 56 months, mortality was lower in the transplant cohort (RR, 0.16; P < .0001). Seven-year survival probabilities (95% confidence interval) were 58% (50% to 66%) with transplant and 32% (22% to 41%) with hydroxyurea or interferon. There was a significant survival advantage for hydroxyurea or interferon in the first 4 years after diagnosis and for transplants starting 5.5 years after diagnosis. For transplants done within 1 year of diagnosis, the survival advantage for transplantation began earlier. Survival advantage for transplants was greater and occurred earlier in patients with intermediate- and high-risk prognostic features than in those with low-risk features. This study confirms higher early mortality, but a long-term survival advantage for HLA-identical sibling transplants over hydroxyurea or interferon in CML.
Gale
R P
RP
International Bone Marrow Transplant Registry, Health Policy Institute, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Hehlmann
R
R
Zhang
M J
MJ
Hasford
J
J
Goldman
J M
JM
Heimpel
H
H
Hochhaus
A
A
Klein
J P
JP
Kolb
H J
HJ
McGlave
P B
PB
Passweg
J R
JR
Rowlings
P A
PA
Sobocinski
K A
KA
Horowitz
M M
MM
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D015331:Cohort Studies; D005260:Female; D006650:Histocompatibility Testing; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000627:therapeutic use*; D007372:Interferons / Q000008:administration & dosage / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D013997:Time Factors
D007372:Interferons; D006918:Hydroxyurea